Innate immune responses Flashcards
What are the two main features of the innate immune response?
Non-specific
Rapid - initial response takes a few hours
What are the molecules involved in the innate immune response?
Antimicrobial peptides
Complement
What are the cells involved in the innate immune response?
Phagocytes
Natural Killer Cells
Interferons
What are the four host defences?
Anatomical and chemical barriers
Intrinsic
Innate immunity
Acquired immunity
What are the anatomical and chemical barriers preventing pathogens from causing disease?
Skin
Mucus
Tears
Preformed soluble molecules
Low pH
Which cells take part in intrinsic immunity?
Always present in all uninfected cells
They have the ability to prevent viruses from getting into the cell
Which processes form part of the intrinsic immunity?
Autophagy
RNA silencing
Antiviral proteins
Apoptosis
Examples of cellular proteins that inhibit viral replication
TRIM
APOBEC3
Tetherin
Examples of soluble mechanisms of innate immunity
Antimicrobial enzymes
Antimicrobial proteins
Complement
Cytokines
Acute phase proteins
Examples of antimicrobial proteins
Defensins
Cathelicidins
Histatins
How do defensins provide immunity?
Small cationic antimicrobial peptides that enter the negatively charged membrane
Form pores
Leads to a loss of small-molecule gradients
What are the two main structural families of defensins?
Alpha defensins
Beta defensins
Which family of defensins is constitutively expressed?
Alpha defensins
What are the two cellular responses in innate immunity in responser to danger inputs?
Response to threat
Communication to other immune cells
What are the three types of PRRs?
Intracellular
Cell surface
Secreted
Examples of DAMPs
Ion concentration changes
DNA
What type of antigens are recognised by the innate immune system?
Structures shared by classes of microbes
100 receptors = 100 molecules recognised
How many types of receptors recognise antigens that activate the innate immune system?
Around 100
Germline encoded
What type of antigens are recognised by the adaptive immunity?
Specific epitoptes
How many molecules can be recognised by the adaptive immune system?
> 10^7
Receptor genes undergo somatic recombination, leading to a huge diversity in the molecules recognised
What are the two classes of receptors making up the adaptive immune system?
Antibody
TCR
What is the main difference of the recognition potential of the adaptive immunity vs the innate immunity?
The adaptive immune receptors undergo somatic recombination
So although there are two main types of receptors (BCR and TCR), there is high variability in their subtypes
The innate immune receptors do not undergo somatic recombination, and the receptors they produce are used to recognise the different antigens
What are the two main types of PRRs?
Soluble molecules
Cell associated molecules
Examples of soluble PRRs
Pentraxins
Ficolins
Collectins
Complement proteins
Examples of cell associted PRRs
C-type lectins
TLR
Scavenger receptors
NOD like receptors
RIG-like receptors
c-GAS
What is the difference between different cell associated PRRs?
Found in different locations on the cell
Cell surface = C-type lectins, TLR
Inside endosomes = TLR
Cytosolic = NOD like receptors, RIG-like receptors
How are soluble PRRs useful?
Recognise presence of a pathogen in the circulation
Describe the specificity of PRRs
Different PRRs recognise different patterns
Elicit specific responses upon binding to a pattern
Describe TLR signalling
- Ligand engages TLR
- Association of protein kinases to adaptor proteins
- Activation of transcription factors
- Formation of respiratory bursts, cytokines, chmokines, MMPs, antimicrobial peptides
What is the function of IRF?
Interferon regulatory factor
Generally antiviral
What is the function of NFkB?
Generally inflammatory
What are the 3 major classes of cytosol PRRs?
NOD like receptors
RIG like receptors
Cytosolic DNA sensors
What do NOD like receptors recognise?
NOD1/2 recognise the bacterial cell wall
What do RIG like receptors recognise?
Viral RNA
What do cytosolic DNA sensors recognise?
Microbial DNA in the cytoplasm
What are the cells of the innate immunity?
Macrophages
Dendritic cells
Neutrophils
Eosinophils
Basophils
Mast cells
Natural killer cells
What is special about neutrophils, eosinophils and basophils?
They are polymorphonuclear leukocytes
Contain granules that stain in different ways to allow for identification
What happens to macrophages and DCs once stimulated by PRRs?
Increase their antigen presenting capacity
Lead to the development of the adaptive immunity
Describe the process by which phagocytosis destroys pathogens
- Chemotaxis
- Adherence via PAMP recognition
- Cell activation via PRR
- Initiation of phagocytosis
- Phagosome formation
- Phagolysosome formation
- Bacterial killing and digestion
- Release of degradation products
What is the main purpose of opsonisation?
Allows the process of phagocytosis to function more efficiently
How do cells carrying out phagocytosis recognise the microbe?
The microbe is bound to antibodies
The FcR of the phagocytosing cell recognises the Fc portion of the antibody
What three main processes lead to bacterial killing in the phagolysosome?
Enzymes
Reactive oxygen species
Reactive nitrogen species
Examples of ROS
Hydroxyl radical
Superoxide
Oxygen-independent mechanisms of pathogen destruction
Damage to microbial membrane by
- cathepsin G
- defensins
- cationic proteins
- bacteriidial permeability increasing proteins
Splitting of mucopeptide in the bacterial cell wall by lyzosymes
Complex with iron through lactoferrin
Digestion of killed organisms through proteolytic and hydrolytic enzymes
What is phagocytosis?
Ingestion and killing of extracellular microbes
Which cells carry out phagocytosis?
Neutrophils
Monocytes
Macrophages
From which cells are macrophages derived from?
Monocytes
Which are the first cells to respond to infection?
Neutrophils
What type of cell are natural killer cells?
Large granular lymphocytes
Where are natural killer cells found?
In the circulation
What percentage of circulating leykocytes do NK cells make up?
5-20%
NK cells destroy bacteria
TRUE or FALSE
FALSE
Recognise changes in self cells
What do NK cells respond to?
Cells with missing self antigens
Stressed cells
Viral haemagglutinins
Antibody-coated cells
What are the two responses evoked by NK cells?
Cytotoxicity
IFNy release
What are NK cells an important source of?
Interferon gamma
Describe what is meant by ‘NK cells react to cells with abnormal self receptors’
Cells express activator proteins as well as MHC I
MHC I binds to the inhibitory receptors on NK cells, preventing them from causing cell death
In cancer or infected cells, they can overexpress activatory proteins or reduce expression of MHC I
This is detected by NK cells, which cause death of these abnormal cells
What are the mechanisms of NK cell killing?
Granzymes enter target cell via perforin pore or endocytosis
Activation of apoptotic pathways
Which cell links the adaptive and innate immune responses?
Dendritic cells
Which scientist first described Dendritic cells?
Langerhans
What are the two states dendritic cells are found in?
Immature
Mature
Compare the MHC expression between mature and immature DCs
Mature DCs express MHC highly
Immature has low surface MHC
Do mature or immature DCs have high phagocytic activity?
Immature DCs are highly phagocytic
How do DCs become mature?
Through detection of microbial products
Inflammatory cytokines
Damaged host cells
Give a brief overview of the role of DCs in the innate immune response
Immature DCs are found in many tissues
Mature in inflamed tissues following cytokine signals and antigen capture
Mature DCs migrate to lymph nodes and present antigenic peptides to T cells
What type of cells are dendritic cells?
Professional antigen presenting cells
Activate naive T cells
How do NK cells carry out cell death the activation of apoptotic pathways?
FASL on NK cells binds to Fas on target cell
FADD becomes activated upon binding, which turns procaspase-8 into caspase-8
Caspase-8 activates Caspase-3
Caspase-3 leads to apoptosis
What is the marker for mature dendritic cells?
CCR7
Immature DCs are also CCR7+, but also express CCR2,5,6
